natural products

天然产物
  • 文章类型: Journal Article
    乳腺癌是全球最常见的恶性肿瘤,也是女性死亡的主要原因。白术A(AM-A)是一种独特的天然倍半萜内酯,分离自白术(中文称为白术)的根茎。我们的研究表明,AM-A触发了类似于PANoptosis样细胞死亡的特定形式的细胞死亡。进一步的分析表明,AM-A诱导的PANoptosis样细胞死亡与CASP-3/PARP-GSDMD-MLKL途径有关,由线粒体功能障碍介导。这些结果表明了AM-A作为先导化合物的潜力,并为从天然产物开发乳腺癌治疗剂提供了见解。
    Breast cancer is the most common malignant tumor and a major cause of mortality among women worldwide. Atramacronoid A (AM-A) is a unique natural sesquiterpene lactone isolated from the rhizome of Atractylodes macrocephala Koidz (known as Baizhu in Chinese). Our study demonstrated that AM-A triggers a specific form of cell death resembling PANoptosis-like cell death. Further analysis indicated that AM-A-induced PANoptosis-like cell death is associated with the CASP-3/PARP-GSDMD-MLKL pathways, which are mediated by mitochondrial dysfunction. These results suggest the potential of AM-A as a lead compound and offer insights for the development of therapeutic agents for breast cancer from natural products.
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  • 文章类型: Journal Article
    Boswelliasacra具有激活血液循环的特性,修复疼痛,减轻肿胀和促进肌肉生长。然而,Boswelliasacra的抗炎活性成分和分子机制尚不清楚。将Boswelliasacra接地并使用95%乙醇提取,通过柱色谱制备分离提取物以得到化合物。光谱分析和量子计算证实了化合物的结构,并确定化合物1为新化合物。化合物1-3显示出有效的抑制活性,并通过ELISA测定法检查其对炎症介质NO和炎症细胞因子的作用。此外,探讨了它们对炎症信号通路的调节机制。
    Boswellia sacra has the properties of activating blood circulation, fixing pain, subduing swelling and promoting muscle growth. However, the anti-inflammatory active ingredients and molecular mechanisms of Boswellia sacra are still not clearly explored. Boswellia sacra was grounded and extracted using 95% ethanol, the extracts were separated by column chromatography preparation to give compounds. Spectral analysis and quantum calculations confirmed the structures of compounds and identified compound 1 as a new compound. Compounds 1-3 showed potent inhibitory activities and their effects on inflammatory mediator NO and inflammatory cytokines were examined by ELISA assay. Furthermore, their modulatory mechanism on inflammatory signal pathways was explored.
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  • 文章类型: Journal Article
    生物膜相关感染仍然是全球微生物感染治疗的巨大障碍。然而,传统抗菌剂对致密胞外聚合物基质的渗透性差限制了它们的抗生物膜活性。这里,我们表明,由两亲性冰片-胍基阳离子聚合物(BGNx-n)自组装形成的纳米聚集体具有很强的抗菌活性,可以消除成熟的金黄色葡萄球菌(S.金黄色葡萄球菌)生物膜。胍部分的引入改善了BGNx-n的亲水性和膜穿透性。具有高度局部化正电荷的自组装纳米聚集体预期增强其与带负电荷的细菌和生物膜的相互作用。此外,纳米聚集体在生物膜表面解离成更小的BGNx-n聚合物,这增强了它们穿透生物膜的能力。表现出优异抗菌活性的BGNx-n纳米聚集体对金黄色葡萄球菌的最小抑制浓度(MIC)为62.5μg·mL-1,并在4×MIC下根除成熟的生物膜,溶血可忽略不计。一起来看,这种大小可变的自组装系统为开发有效的抗生物膜剂提供了有希望的策略。
    Biofilm-associated infections remain a tremendous obstacle to the treatment of microbial infections globally. However, the poor penetrability to a dense extracellular polymeric substance matrix of traditional antibacterial agents limits their antibiofilm activity. Here, we show that nanoaggregates formed by self-assembly of amphiphilic borneol-guanidine-based cationic polymers (BGNx-n) possess strong antibacterial activity and can eliminate mature Staphylococcus aureus (S. aureus) biofilms. The introduction of the guanidine moiety improves the hydrophilicity and membrane penetrability of BGNx-n. The self-assembled nanoaggregates with highly localized positive charges are expected to enhance their interaction with negatively charged bacteria and biofilms. Furthermore, nanoaggregates dissociate on the surface of biofilms into smaller BGNx-n polymers, which enhances their ability to penetrate biofilms. BGNx-n nanoaggregates that exhibit superior antibacterial activity have the minimum inhibitory concentration (MIC) of 62.5 μg·mL-1 against S. aureus and eradicate mature biofilms at 4 × MIC with negligible hemolysis. Taken together, this size-variable self-assembly system offers a promising strategy for the development of effective antibiofilm agents.
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  • 文章类型: Journal Article
    越来越多的证据表明,微生物合成在生产高附加值产品中起着重要作用。然而,由于宿主菌株的代谢负担增加,微生物单一培养通常会阻碍代谢物的产生并限制可扩展性。相比之下,共培养是一种更灵活的方法,可以提高环境适应性,降低整体代谢负担。定义明确的共培养微生物聚生体可以挖掘其代谢潜力,以获得尚未发现的和预先存在的代谢物。这篇综述的重点是使用共同文化战略及其潜在机制来提高产品的生产。值得注意的是,理解微生物相互作用的重要性,不同的沟通方式,遗传信息,强调了共同培养系统中涉及的模块化共同培养。此外,它解决了当前的挑战,并概述了微生物共培养的潜在未来方向。这篇综述提供了更好地了解有趣的互动和交流的多样性和复杂性,以促进共同文化技术的发展。
    Increasing evidence shows that microbial synthesis plays an important role in producing high value-added products. However, microbial monoculture generally hampers metabolites production and limits scalability due to the increased metabolic burden on the host strain. In contrast, co-culture is a more flexible approach to improve the environmental adaptability and reduce the overall metabolic burden. The well-defined co-culturing microbial consortia can tap their metabolic potential to obtain yet-to-be discovered and pre-existing metabolites. This review focuses on the use of a co-culture strategy and its underlying mechanisms to enhance the production of products. Notably, the significance of comprehending the microbial interactions, diverse communication modes, genetic information, and modular co-culture involved in co-culture systems were highlighted. Furthermore, it addresses the current challenges and outlines potential future directions for microbial co-culture. This review provides better understanding the diversity and complexity of the interesting interaction and communication to advance the development of co-culture techniques.
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  • 文章类型: Journal Article
    芳香族氨基酸(AAA)及其衍生化合物具有巨大的商业价值,在食品中有着广泛的应用,化学和制药领域。AAA及其衍生化合物的微生物生产因其环境友好性和可持续性而具有广阔的前景。然而,低产量和生产效率仍然是实现工业生产的主要挑战。随着合成生物学的发展,AAA和衍生化合物的微生物生产得到了显著促进。在这次审查中,对当前进展的全面概述,提供了AAA和衍生化合物生物合成的挑战和相应的解决方案。AAA和衍生化合物生物合成中合成生物学技术的最前沿发展,包括基于CRISPR的系统,基因编码的生物传感器和合成遗传电路,被突出显示。最后,讨论了有利于AAA和衍生化合物生物合成的现代策略的未来前景。本综述为利用合成生物学技术构建芳香化合物微生物细胞工厂提供指导。
    Aromatic amino acids (AAA) and derived compounds have enormous commercial value with extensive applications in the food, chemical and pharmaceutical fields. Microbial production of AAA and derived compounds is a promising prospect for its environmental friendliness and sustainability. However, low yield and production efficiency remain major challenges for realizing industrial production. With the advancement of synthetic biology, microbial production of AAA and derived compounds has been significantly facilitated. In this review, a comprehensive overview on the current progresses, challenges and corresponding solutions for AAA and derived compounds biosynthesis is provided. The most cutting-edge developments of synthetic biology technology in AAA and derived compounds biosynthesis, including CRISPR-based system, genetically encoded biosensors and synthetic genetic circuits, were highlighted. Finally, future prospects of modern strategies conducive to the biosynthesis of AAA and derived compounds are discussed. This review offers guidance on constructing microbial cell factory for aromatic compound using synthetic biology technology.
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  • 文章类型: Journal Article
    在开发易于细菌定殖和生物膜形成的生物医学装置的惰性表面的抗感染涂层方面仍然存在挑战。这里,我们开发了一种简便的光固化方法来在惰性PDMS表面上构建功能化的聚合物涂层。使用带有百里酚基团的ATRP引发剂,将亲水性DMAEMA和含二苯甲酮的单体共聚形成具有末端官能团的聚合物。然后使用光固化反应在一个步骤中在惰性PDMS表面上构建末端官能化的杀生物涂层。功能化的PDMS表面表现出优异的抗菌和防污性能,能够在大约6小时内完全消除MRSA,并有效抑制生物膜的生长。此外,在0.9%生理盐水和尿液等体液环境中具有良好的稳定性和持久的抗菌活性。根据膀胱模型实验,通过抑制细菌沿着导管内表面的生长和迁移,导管的寿命可以从大约7天延长到35天。因此,光固化技术在惰性生物医学装置的表面官能化方面是非常有前途的,以便最小化感染的扩散。本文受版权保护。保留所有权利。
    A challenge remains in the development of anti-infectious coatings for the inert surfaces of biomedical devices that are prone to bacterial colonization and biofilm formation. Here, a facile photocuring method to construct functionalized polymeric coatings on inert polydimethylsiloxane (PDMS) surfaces, is developed. Using atom transfer radical polymerization (ATRP) initiator bearing thymol group, hydrophilic DMAEMA and benzophenone (BP)-containing monomers are copolymerized to form polymers with end functional groups. An end-functionalized biocidal coating is then constructed on the inert PDMS surface in one step using a photocuring reaction. The functionalized PDMS surfaces show excellent antibacterial and antifouling properties, are capable of completely eradiating MRSA within ≈6 h, and effectively inhibit the growth of biofilms. In addition, they have good stability and long-lasting antibacterial activity in body fluid environments such as 0.9% saline and urine. According to bladder model experiments, the catheter\'s lifespan can be extended from ≈7 to 35 days by inhibiting the growth and migration of bacteria along its inner surface. The photocuring technique is therefore very promising in terms of surface functionalization of inert biomedical devices in order to minimize the spread of infection.
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  • 文章类型: Journal Article
    在肿瘤纳米医学中,克服肿瘤微环境中的双相高间质压力对于增强纳米治疗剂的渗透和功效至关重要。肿瘤间质实体压(TISP)升高主要归因于细胞外基质中胶原蛋白的过度积累,而肿瘤间质液压力(TIFP)的增加源于异常血管结构引起的液体积聚。在这种情况下,具有催化效率的金属有机框架(MOFs)已显示出降解肿瘤间质成分的潜力,从而降低间隙压力。然而,MOFs有机成分的潜在生物毒性限制了其临床转化。为了避免这种情况,类似MOF的光催化纳米酶,RPC@M,使用天然来源的植酸钴(CoPA)和白藜芦醇(Res)开发。这种纳米酶不仅促进肿瘤间质中的水在光活化下分解以减少TIFP,而且还通过其过氧化物酶样活性产生大量的活性氧,对肿瘤细胞发挥细胞毒性作用。此外,Res有助于减少胶原蛋白沉积,从而降低了TISP。RPC@M同时减少TISP和TIFP导致肿瘤渗透增强和有效的抗肿瘤活性,提出了一种从天然产物构建肿瘤治疗纳米酶的创新方法。
    In oncological nanomedicine, overcoming the dual-phase high interstitial pressure in the tumor microenvironment is pivotal for enhancing the penetration and efficacy of nanotherapeutics. The elevated tumor interstitial solid pressure (TISP) is largely attributed to the overaccumulation of collagen in the extracellular matrix, while the increased tumor interstitial fluid pressure (TIFP) stems from the accumulation of fluid due to the aberrant vascular architecture. In this context, metal-organic frameworks (MOFs) with catalytic efficiency have shown potential in degrading tumor interstitial components, thereby reducing interstitial pressure. However, the potential biotoxicity of the organic components of MOFs limits their clinical translation. To circumvent this, a MOF-like photocatalytic nanozyme, RPC@M, using naturally derived cobalt phytate (CoPA) and resveratrol (Res) is developed. This nanozyme not only facilitates the decomposition of water in the tumor interstitium under photoactivation to reduce TIFP, but also generates an abundance of reactive oxygen species through its peroxidase-like activity to exert cytotoxic effects on tumor cells. Moreover, Res contributes to the reduction of collagen deposition, thereby lowering TISP. The concurrent diminution of both TISP and TIFP by RPC@M leads to enhanced tumor penetration and potent antitumor activity, presenting an innovative approach in constructing tumor therapeutic nanozymes from natural products.
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  • 文章类型: Journal Article
    目前,估计有5.37亿人患有2型糖尿病(T2DM),其发生总是与并发症有关。降糖治疗仍是缓解T2DM的主要治疗手段。然而,传统的抗糖尿病药物充满了许多副作用,尤其是血压和血脂水平升高。最近,使用中药(TCMs)及其成分已成为一种首选的治疗策略,旨在减少糖尿病及其相关并发症的进展,减少不良反应.越来越多的证据表明,肠道微生物群紊乱与T2DM及其并发症的发生有关。这种调节取决于肠道微生物产生的各种代谢物及其与宿主器官的相互作用。TCM干预已经证明了调节肠道细菌微生物群的能力,从而恢复宿主稳态和改善代谢紊乱。这篇综述探讨了T2DM患者肠道菌群和代谢产物的变化,以及TCM治疗如何调节肠道菌群。促进T2DM及其并发症的管理。此外,我们还讨论了研究天然产品以促进糖尿病治疗的前瞻性途径。
    Currently, an estimated 537 million individuals are affected by type 2 diabetes mellitus (T2DM), the occurrence of which is invariably associated with complications. Glucose-lowering therapy remains the main treatment for alleviating T2DM. However, conventional antidiabetic agents are fraught with numerous adverse effects, notably elevations in blood pressure and lipid levels. Recently, the use of traditional Chinese medicines (TCMs) and their constituents has emerged as a preferred management strategy aimed at curtailing the progression of diabetes and its associated complications with fewer adverse effects. Increasing evidence indicates that gut microbiome disturbances are involved in the development of T2DM and its complications. This regulation depends on various metabolites produced by gut microbes and their interactions with host organs. TCMs\' interventions have demonstrated the ability to modulate the intestinal bacterial microbiota, thereby restoring host homeostasis and ameliorating metabolic disorders. This review delves into the alterations in the gut microbiota and metabolites in T2DM patients and how TCMs treatment regulates the gut microbiota, facilitating the management of T2DM and its complications. Additionally, we also discuss prospective avenues for research on natural products to advance diabetes therapy.
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  • 文章类型: Journal Article
    糖尿病视网膜病变(DR)是糖尿病最严重的并发症之一,可能导致严重的视力障碍和失明。DR病理变化中涉及的复杂机制使现有治疗方法取得令人满意的结果具有挑战性。有助于血糖控制的饮食已被证明可以改善糖尿病患者的预后。因此将饮食干预定位为DR治疗的有希望的途径.研究表明,天然产物(NPs)可以有效地管理DR。许多类型的天然化合物,包括皂苷,酚类物质,萜类化合物,黄酮类化合物,糖类,生物碱,和维生素,已经被证明具有抗炎作用,抗氧化剂,抗新生血管,体内和体外抗凋亡作用。然而,NPs的临床应用仍然面临挑战,例如次优特异性,生物利用度差,和毒性的风险。前瞻性临床研究对于验证NPs在延迟或预防DR方面的治疗潜力至关重要。
    Diabetic retinopathy (DR) is one of the most severe complications of diabetes mellitus and potentially leads to significant visual impairment and blindness. The complex mechanisms involved in the pathological changes in DR make it challenging to achieve satisfactory outcomes with existing treatments. Diets conducive to glycemic control have been shown to improve outcomes in diabetic patients, thus positioning dietary interventions as promising avenues for DR treatment. Investigations have demonstrated that natural products (NPs) may effectively manage DR. Many types of natural compounds, including saponins, phenols, terpenoids, flavonoids, saccharides, alkaloids, and vitamins, have been shown to exert anti-inflammatory, antioxidant, anti-neovascular, and antiapoptotic effects in vivo and in vitro. Nevertheless, the clinical application of NPs still faces challenges, such as suboptimal specificity, poor bioavailability, and a risk of toxicity. Prospective clinical studies are imperative to validate the therapeutic potential of NPs in delaying or preventing DR.
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  • 文章类型: Journal Article
    毛囊发育和毛发生长受多种因素和多种信号通路调节。毛囊,作为重要的皮肤附属物,是头发生长的基础,它具有保护身体的功能,感知环境和调节体温。头发生长经历一个有规律的头发周期,包括生长期,capagen和talogen.在正常情况下,会发生少量的生理性毛发脱落,总是处于动态平衡状态。当皮肤或毛囊受到氧化应激刺激时,就会发生脱发,炎症或激素紊乱,破坏毛囊的稳态。大量研究表明,氧化应激是引起脱发的重要因素。这里,我们总结了氧化应激影响毛囊发育和毛发生长的信号通路和干预机制,通过抗氧化剂途径讨论现有的脱发治疗方法,并提供我们自己的见解。此外,我们整理了近年来促进头发生长的抗氧化天然产物,并讨论了当前脱发预防和治疗的局限性和观点。
    Hair follicle development and hair growth are regulated by multiple factors and multiple signalling pathways. The hair follicle, as an important skin appendage, is the basis for hair growth, and it has the functions of safeguarding the body, perceiving the environment and regulating body temperature. Hair growth undergoes a regular hair cycle, including anagen, catagen and telogen. A small amount of physiological shedding of hair occurs under normal conditions, always in a dynamic equilibrium. Hair loss occurs when the skin or hair follicles are stimulated by oxidative stress, inflammation or hormonal disorders that disrupt the homeostasis of the hair follicles. Numerous researches have indicated that oxidative stress is an important factor causing hair loss. Here, we summarize the signalling pathways and intervention mechanisms by which oxidative stress affects hair follicle development and hair growth, discuss existing treatments for hair loss via the antioxidant pathway and provide our own insights. In addition, we collate antioxidant natural products promoting hair growth in recent years and discuss the limitations and perspectives of current hair loss prevention and treatment.
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